SNP Shot: Genomic Insights

Megalencephaly-capillary malformation syndrome (MCAP) is a condition marked by excessive growth in various body tissues. Key signs include an enlarged brain (megalencephaly) and abnormalities in the skin's small blood vessels (capillary malformations).

In those with MCAP, megalencephaly results in an unusually large head size (macrocephaly), typically noticeable at birth. Following birth, the brain and head grow rapidly for the first few years, then slow to a normal rate, though the head remains larger than average. Other brain issues are common in MCAP, such as excess fluid in the brain (hydrocephalus) and structural abnormalities like Chiari malformation and polymicrogyria. Abnormal brain development often leads to intellectual disability and can also cause seizures or weak muscle tone (hypotonia). Polymicrogyria, in particular, is linked to speech delays and difficulty with chewing and swallowing.

The capillary malformations typical of MCAP consist of enlarged capillaries, increasing blood flow near the skin's surface. These appear as pink or red spots on the skin. Often, these malformations are on the face, especially the nose, upper lip, and the area between the nose and lip (philtrum). In others, the malformations present as patches spread across the body or as a reddish, net-like pattern on the skin (cutis marmorata).

Some individuals with MCAP experience excessive growth beyond the brain, affecting specific body parts, which is called segmental overgrowth. This can result in one arm or leg being larger or longer than the other, or a few oversized fingers or toes. Some also have fused skin between fingers or toes (cutaneous syndactyly).

Other features of MCAP can include flexible joints and easily stretched skin. Some are described as having doughy skin due to unusually thick and soft tissue under the skin.

The gene associated with MCAP is also linked to several cancers. Only a small number of people with MCAP have developed tumors, specifically Wilms tumor (a childhood kidney cancer) and noncancerous nervous system tumors (meningiomas).

Inheritance:

MCAP is not inherited and doesn't run in families. In individuals with MCAP, a PIK3CA gene mutation occurs randomly in a single cell during early development before birth. As cells divide, some will carry the mutation, and others won't. This mixture of cells with and without the mutation is called mosaicism.